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  • 1
    Publication Date: 2017-01-26
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev , info:eu-repo/semantics/article
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 14 (2000), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The polypeptide hormone gastrin was identified nearly a hundred years ago and its role in the regulation of acid secretion is well established. Gastrin also acts as a growth factor and is trophic for the normal gastric oxyntic mucosa. This growth promoting action has led to the extensive investigation of its role in carcinogenesis, in particular colorectal neoplasia. The relationship between gastrin and colorectal adenocarcinoma has been subject to controversy, however the findings from several recent studies have resulted in a clearer understanding of the mechanism of action of gastrin in this is common cancer.The majority of colorectal cancers produce their own gastrin, which may act in an autocrine manner. The tumour cells also express gastrin/CCKB receptors (and/or a combination of isoforms) which mediate the proliferative action. This locally produced gastrin gives rise to a small increase in systemic gastrin levels. Autocrine gastrin may also have a role in tumour development, as expression occurs early in the adenoma–carcinoma sequence. In addition, several studies using animal models have shown that systemic hypergastrinaemia promotes the proliferation of both normal and neoplastic colonic epithelium. Hyperproliferative colonic epithelium in the presence of hypergastrinaemia has been recorded in humans and a well-designed epidemiological study has demonstrated an increased incidence of colorectal cancer.Gastrin is a potential therapeutic target in the treatment of colorectal cancer and several approaches have been assessed. Receptor antagonists and antisecretory agents have been demonstrated to be ineffectual. Novel methods of inhibition, including the use of anti-gastrin antibodies, are currently being evaluated.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 15 (2001), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Gastrimmune is an immunogenic form of gastrin. It raises in situ antibodies against two proliferative forms of gastrin: amidated and glycine-extended gastrin-17. It has been shown to have a therapeutic action in several in vivo tumour models. Following immunization, due to the complex equilibrium that exists between the antibodies and gastrin, it is not technically feasible to assay for free gastrin.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To determine the effect of Gastrimmune-induced antigastrin antibodies on acid secretion.〈section xml:id="abs1-3"〉〈title type="main"〉Method:A rat gastric fistula model was used. Animals (six per group) were immunized with a control immunogen or ascending doses of Gastrimmune. Acid output was measured following infusion of increasing doses of gastrin-17 and pentagastrin.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Gastrimmune-induced antibodies significantly reduced gastrin-17-stimulated acid output compared to control animals (Gastrimmune at 200 μg/rat vs. control; acid output following 30 ng gastrin-17, 0.01 vs. 0.16, P 〈 0.001; following 120 ng gastrin-17, 0.022 vs. 0.29, P 〈 0.001).〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Gastrimmune significantly inhibits gastrin-17-stimulated acid output. This biological assay suggests that the antigastrin antibodies effectively bind gastrin-17. In addition to its use as an antineoplastic agent, Gastrimmune may have a role as an acid-decreasing agent in oesophagogastric pathology.
    Type of Medium: Electronic Resource
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  • 4
    Publication Date: 2016-02-27
    Description: Changes in environmental conditions, such as those caused by elevated carbon dioxide (CO 2 ), potentially alter the outcome of competitive interactions between species. This study aimed to understand how elevated CO 2 could influence competitive interactions between hard and soft corals, by investigating growth and photosynthetic activity of Porites cylindrica (a hard coral) under elevated CO 2 and in the presence of another hard coral and two soft coral competitors. Corals were collected from reefs around Orpheus and Pelorus Islands on the Great Barrier Reef, Australia. They were then exposed to elevated p CO 2 for 4 weeks with two CO 2 treatments: intermediate ( p CO 2 648) and high ( p CO 2 1003) compared with a control (unmanipulated seawater) treatment ( p CO 2 358). Porites cylindrica growth did not vary among p CO 2 treatments, regardless of the presence and type of competitors, nor was the growth of another hard coral species, Acropora cerealis , affected by p CO 2 treatment. Photosynthetic rates of P. cylindrica were sensitive to variations in p CO 2 , and varied between the side of the fragment facing the competitors vs. the side facing away from the competitor. However, variation in photosynthetic rates depended on p CO 2 treatment, competitor identity, and whether the photosynthetic yields were measured as maximum or effective photosynthetic yield. This study suggests that elevated CO 2 may impair photosynthetic activity, but not growth, of a hard coral under competition and confirms the hypothesis that soft corals are generally resistant to elevated CO 2 . Overall, our results indicate that shifts in the species composition in coral communities as a result of elevated CO 2 could be more strongly related to the individual tolerance of different species rather than a result of competitive interactions between species.
    Print ISSN: 1054-3139
    Electronic ISSN: 1095-9289
    Topics: Biology , Geosciences , Physics
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  • 5
    Publication Date: 2016-02-27
    Description: An increasing number of studies have examined the effects of elevated carbon dioxide (CO 2 ) and ocean acidification on marine fish, yet little is known about the effects on large pelagic fish. We tested the effects of elevated CO 2 on the early life history development and behaviour of yellowtail kingfish, Seriola lalandi . Eggs and larvae were reared in current day control (450 µatm) and two elevated CO 2 treatments for a total of 6 d, from 12 h post-fertilization until 3 d post-hatching (dph). Elevated CO 2 treatments matched projections for the open ocean by the year 2100 under RCP 8.5 (880 µatm CO 2 ) and a higher level (1700 µatm CO 2 ) relevant to upwelling zones where pelagic fish often spawn. There was no effect of elevated CO 2 on survival to hatching or 3 dph. Oil globule diameter decreased with an increasing CO 2 level, indicating potential effects of elevated CO 2 on energy utilization of newly hatched larvae, but other morphometric traits did not differ among treatments. Contrary to expectations, there were no effects of elevated CO 2 on larval behaviour. Activity level, startle response, and phototaxis did not differ among treatments. Our results contrast with findings for reef fish, where a wide range of sensory and behavioural effects have been reported. We hypothesize that the absence of behavioural effects in 3 dph yellowtail kingfish is due to the early developmental state of newly hatched pelagic fish. Behavioural effects of high CO 2 may not occur until larvae commence branchial acid–base regulation when the gills develop; however, further studies are required to test this hypothesis. Our results suggest that the early stages of kingfish development are tolerant to rising CO 2 levels in the ocean.
    Print ISSN: 1054-3139
    Electronic ISSN: 1095-9289
    Topics: Biology , Geosciences , Physics
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  • 6
    Publication Date: 2016-09-23
    Print ISSN: 0008-6363
    Electronic ISSN: 1755-3245
    Topics: Medicine
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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2017-09-21
    Description: The proportion of body mass devoted to skeleton in marine invertebrates decreases along latitudinal gradients from large proportions in the tropics to small proportions in polar regions. A historical hypothesis—that latitudinal differences in shell production costs explain these trends—remains untested. Using field-collected specimens spanning a 79°N to 68°S latitudinal gradient (16,300 km), we conducted a taxonomically controlled evaluation of energetic costs of shell production as a proportion of the total energy budget in mollusks. Shell production cost was fairly low across latitudes at 〈10% of the energy budget and predominately 〈5% in gastropods and 〈4% in bivalves. Throughout life, shell cost tended to be lower in tropical species and increased slightly toward the poles. However, shell cost also varied with life stage, with the greatest costs found in young tropical gastropods. Low shell production costs on the energy budget suggest that shell cost may play only a small role in influencing proportional skeleton size gradients across latitudes relative to other ecological factors, such as predation in present-day oceans. However, any increase in the cost of calcium carbonate (CaCO 3 ) deposition, including from ocean acidification, may lead to a projected ~50 to 70% increase in the proportion of the total energy budget required for shell production for a doubling of the CaCO 3 deposition cost. Changes in energy budget allocation to shell cost would likely alter ecological trade-offs between calcification and other drivers, such as predation, in marine ecosystems.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 8
    Publication Date: 2012-11-17
    Description: VEGF plays a central role in angiogenesis in cancer. Non-small cell lung cancer (NSCLC) tumors have increased microvascular density, localized hypoxia, and high VEGF expression levels; however, there is a lack of understanding of how oncogenic and tumor microenvironment changes such as hypoxia lead to greater VEGF expression in lung and other cancers. We show that NSCLC cells secreted higher levels of VEGF than normal airway epithelial cells. Actinomycin D inhibited all NSCLC VEGF secretion, and VEGF minimal promoter-luciferase reporter constructs were constitutively active until the last 85 base pairs before the transcription start site containing three SP-1 transcription factor-binding sites; mutation of these VEGF promoter SP-1-binding sites eliminated VEGF promoter activity. Furthermore, dominant negative SP-1, mithramycin A, and SP-1 shRNA decreased VEGF promoter activity, whereas overexpression of SP-1 increased VEGF promoter activity. Chromatin immunoprecipitation assays demonstrated SP-1, p300, and PCA/F histone acetyltransferase binding and histone H4 hyperacetylation at the VEGF promoter in NSCLC cells. Cultured NSCLC cells expressed higher levels of SP-1 protein than normal airway epithelial cells, and double-fluorescence immunohistochemistry showed a strong correlation between SP-1 and VEGF in human NSCLC tumors. In addition, hypoxia-driven VEGF expression in NSCLC cells was SP-1-dependent, with hypoxia increasing SP-1 activity and binding to the VEGF promoter. These studies are the first to demonstrate that overexpression of SP-1 plays a central role in hypoxia-induced VEGF secretion.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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  • 9
    Publication Date: 2016-02-27
    Description: Increased oceanic uptake of atmospheric carbon dioxide (CO 2 ) is a threat to marine organisms and ecosystems. Among the most dramatic consequences predicted to date are behavioural impairments in marine fish which appear to be caused by the interference of elevated CO 2 with a key neurotransmitter receptor in the brain. In this study, we tested the effects of elevated CO 2 on the foraging and shelter-seeking behaviours of the reef-dwelling epaulette shark, Hemiscyllium ocellatum . Juvenile sharks were exposed for 30 d to control CO 2 (400 µatm) and two elevated CO 2 treatments (615 and 910 µatm), consistent with medium- and high-end projections for ocean p CO 2 by 2100. Contrary to the effects observed in teleosts and in some other sharks, behaviour of the epaulette shark was unaffected by elevated CO 2 . A potential explanation is the remarkable adaptation of H. ocellatum to low environmental oxygen conditions (hypoxia) and diel fluctuations in CO 2 encountered in their shallow reef habitat. This ability translates into behavioural tolerance of near-future ocean acidification, suggesting that behavioural tolerance and subsequent adaptation to projected future CO 2 levels might be possible in some other fish, if adaptation can keep pace with the rate of rising CO 2 levels.
    Print ISSN: 1054-3139
    Electronic ISSN: 1095-9289
    Topics: Biology , Geosciences , Physics
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